Patent RU-2661197-C2 (RU)
Inventor: BEJKER-GLENN Charlz
IPC: C07D413/12
Filed: 2012-11-28
Granted: 2018-07-13
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention relates to novel compounds of formula I and formula II or pharmaceutically acceptable salts thereof, having the properties of a leucine repeat kinase inhibitor 2 (LRRK2, id est "Leucine Rich Repeat Kinase"). Compounds of formula I and formula II correspond to structures 
     
       
     
     or    
     In the compound of formula I, m is 0, 1 or 2; X is -NR a - or -O-, and R a  represents a hydrogen atom or C 1-6 alkyl; R 1  is C 1-6 alkyl or C 3-6 cycloalkyl optionally substituted with a halogen atom, or, if X is NH, R 1  is deuterated C 3-6 cycloalkyl; or R 1  and R a  together with the atoms to which they are attached, can form a three-six-membered ring; R 2  is a halogen atom, cyano or halo-C 1-6 alkyl; R 3  is -OR 4 , a halogen atom or C 1-6 alkyl; R 4  is a hydrogen atom, C 1-6 alkyl, halogen-C 1-6 alkyl, C 3-6 cycloalkyl or C 3-6 cycloalkyl-C 1-6 alkyl; R 5  is a hydrogen atom or C 1-6 alkyl; R 6  is a hydrogen atom, C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 3-6 cycloalkyl-C 1-6 alkyl, optionally substituted with hydroxy, 5-6 membered heteroaryl or heterocyclyl with 1 to 2 nitrogen atoms as ring heteroatoms; where heteroaryl and heterocyclyl each may be optionally substituted with C 1-6 alkyl; or R 5  and R 6  together with the nitrogen atom to which they are attached, form a four-seven-membered ring, optionally including an additional heteroatom selected from O and N, and optionally substituted with one or two groups independently selected from the following groups: C 1-6 alkyl, C 1-6 alkoxy, halogen-C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, hydroxy-C 1-6 alkyl, halogen atom, C 3-6 cycloalkyl-C 1-6 alkyl and 4-6 membered heterocyclyl with 1 to 2 heteroatoms selected from N and O; or R 5  and R 6  together with the nitrogen atom to which they are attached, and an additional heteroatom O form a deuterated morpholino group; or hexahydro-pyrrolo [1,2-a]pyrazinyl, 8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl, 2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl, 1-oxa-6-aza-spiro[3.3]hept-6-yl or 2-oxa-6-aza-spiro[3.3]hept-6-yl; and R 7  is a hydroxy group, a halogen atom, C 1-6 alkyl, C 1-6 alkoxy, halogen-C 1-6 alkyl or halogen-C 1-6 alkoxy; wherein said compound is selected from the group of compounds indicated in claim 1 of the invention. Preferably such a compound may be [4-(4-cyclopropylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-phenyl]-morpholin-4-yl-methanone or [4-(4-cyclopropylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-5-methoxy-2-methyl-phenyl]-morpholin-4-yl-methanone. In the compound of formula II, A is a five- or six-membered ring containing one or two heteroatoms, each independently selected from O; m is 0, 1 or 2; X is -NR a - or -O-, and R a  represents a hydrogen atom or C 1-6 alkyl; R 1  is C 1-6 alkyl or C 3-6 cycloalkyl; or R 1  and R a  together with the atoms to which they are attached, can form a three-six-membered ring; R 2  is a halogen atom, cyano or halo-C 1-6 alkyl; R 5  is a hydrogen atom or C 1-6 alkyl; R 6  is a hydrogen atom, C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 3-6 cycloalkyl-C 1-6 alkyl or heterocyclyl with 1 to 2 nitrogen atoms as heteroatoms in the ring, where heterocyclyl may be optionally substituted with C 1-6 alkyl; or R 5  and R 6  together with the nitrogen atom to which they are attached, form a four to six membered ring optionally including an additional heteroatom selected from O or N, and optionally substituted with one or two groups independently selected from the following groups: C 1-6 alkyl, C 1-6 alkoxy, halogen-C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, hydroxy-C 1-6 alkyl, halogen atom, C 3-6 cycloalkyl-C 1-6 alkyl and 4-6 membered heterocyclyl with 1 to 2 heteroatoms selected from N and O; or hexahydro-pyrrolo[1,2-a]pyrazinyl, 8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl, 2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl, 1-oxa-6-aza-spiro[3.3]hept-6-yl or 2-oxa-6-aza-spiro [3.3] hept-6-yl; and R 7  is a halogen atom, C 1-6 alkyl, C 1-6 alkoxy, halogen-C 1-6 alkyl or halogen-C 1-6 alkoxy. 
     EFFECT: compounds can be used to treat Parkinson's disease mediated by the activity of said kinase. 
     11 cl, 6 tbl, 20 ex